Data from our laboratory have shown that nerve growth factor is synthesized and secreted by a variety of normal and transformed cells in culture. The function of cell-derived nerve growth factor is not known although it is possible that peripheral tissues produce the protein to support sensory and sympathetic neurons. Recent studies indicate that central nervous system glioma cells as well as skeletal muscle cells also produce a form of nerve growth factor in culture. These cells interact with brain and spinal cord neurons and it could be that nerve growth factor has functions in the central nervous system. Using chemical and biological methods, we propose to: (1) collect, isolate, and characterize the nerve growth factor which is produced by glioma cells and skeletal muscle cells; (2) assay the effects of these substances on the development of brain and spinal cord neurons in culture; (3) begin to develop histochemical techniques by which nerve growth factor can be localized in neural and non-neural tissues.